This Week in Science

Science  31 Mar 2017:
Vol. 355, Issue 6332, pp. 1386
  1. Drug Development

    Small molecules to target parasite organelle

    1. Caroline Ash

    Colorized scanning electron micrograph of a Trypanosoma brucei parasite (blue) in a mouse liver.

    CREDIT: UNIVERSITÉ LIBRE DE BRUXELLES/SCIENCE SOURCE

    The glycosome is a peroxisome-like organelle that packages glycolytic enzymes of the parasites that cause sleeping sickness, Chagas disease, and leishmaniases. Dawidowski et al. designed small-molecule inhibitors to disrupt interactions between two of the proteins involved in peroxisome biogenesis (PEX5 and PEX14), which permit import of glycosomal matrix proteins from the cytoplasm. The small peptide–mimicking molecules kill the trypanosome parasites by causing metabolic collapse without interfering with human PEX homologs. Preliminary studies in mice confirmed an antiparasitic effect.

    Science, this issue p. 1416

  2. Immunotherapy

    CD28 is a critical target for PD-1 blockade

    1. Priscilla N. Kelly

    PD-1–targeted therapies have been a breakthrough for treating certain tumors and can rejuvenate T cells to unleash the anticancer immune response (see the Perspective by Clouthier and Ohashi). It is widely believed that PD-1 suppresses signaling through the T cell receptor (TCR). However, Hui et al. find instead that the TCR costimulatory receptor, CD28, is the primary target of PD-1 signaling. Independently, Kamphorst et al. show that CD28 is required for PD-1 therapies to kill cancer cells efficiently and eliminate chronic viral infections in mice. Lung cancer patients that responded to PD-1 therapy had more CD28+ T cells, which suggests that CD28 may predict treatment response.

    Science, this issue p. 1428, p. 1423; see also p. 1373

  3. Carbon Cycle

    Digging deeper into soils

    1. H. Jesse Smith

    Soils contain about twice as much carbon as Earth's atmosphere, so their response to warming is crucial to understanding carbon fluxes in a changing climate. Past studies have heated soil to a depth of 5 to 20 cm to examine such fluxes. Hicks Pries et al. heated the ground to a depth of 100 cm. Extending measurements to that depth revealed that 4°C of warming increased annual soil respiration by 34 to 37%—a considerable amount more than previously observed.

    Science, this issue p. 1420

  4. Cometary Science

    The changing surface of a comet

    1. Keith T. Smith

    From 2014 to 2016, the Rosetta spacecraft investigated comet 67P/Churyumov-Gerasimenko as it passed through the inner solar system. El-Maarry et al. compared images of the surface taken before and after the comet's closest approach to the Sun. Numerous geological changes were evident, including cliff collapses, large boulders that moved, and cracks that opened up. These seem to have been triggered by seasonal factors, such as the amount of sunlight falling on each area. Understanding such changes should help elucidate comet formation and evolution.

    Science, this issue p. 1392

  5. Neuroscience

    The calming effect of breathing

    1. Peter Stern

    The rhythmic activity of a cluster of neurons in the brainstem initiates breathing. This cluster is composed of distinct, though intermingled, subgroups of neurons. Yackle et al. found a small, molecularly defined neuronal subpopulation in this breathing rhythm generator that directly projects to a brain center that plays a key role in generalized alertness, attention, and stress (see the Perspective by Sheikhbahaei and Smith). Removal of these cells did not affect normal breathing but left the animals unusually calm. The breathing center thus has a direct and dramatic influence on higher-order brain function.

    Science, this issue p. 1411; see also p. 1370

  6. Immunogenomics

    Aging and variability among immune cells

    1. Laura M. Zahn

    How and why the immune system becomes less effective with age are not well understood. Martinez-Jimenez et al. performed single-cell sequencing of CD4+ T cells in old and young mice of two species. In young mice, the gene expression program of early immune activation was tightly regulated and conserved between species. However, as mice aged, the expression of genes involved in pathways responding to immune cell stimulation was not as robust and exhibited increased cell-to-cell variability.

    Science, this issue p. 1433

  7. Crystal Growth

    Predicting the shape of crystals to come

    1. Marc S. Lavine

    Coral-like structures formed by carbonate and silica

    PHOTO: KAPLAN ET AL.

    Coprecipitating carbonate and silica can form complex three-dimensional shapes. These range from flowers to trumpets, depending on the pH. Kaplan et al. developed a theoretical model to interpret the crystal growth shapes. The model predicts crystal growth shapes under varying experimental conditions and captures the geometrical aspects of morphological development.

    Science, this issue p. 1395

  8. Social Sciences

    Knowing a name promotes cooperation

    1. Cedric Tan

    When people know each other by name, they are more likely to cooperate with one another. Wang et al. looked at the impact of anonymity in the context of “prisoner's dilemma” experiments. In these experiments, two individuals each have the options to betray or cooperate, and the result depends on the choice made by the other person. Cooperation was more common when participants knew their counterpart by name. Participants in this experiment were acquaintances in the same class before the experiment. It thus remains unclear whether factors such as similar age, similar interests, or prior knowledge about one another encouraged cooperation.

    Sci Adv. 10.1126/sciadv.1601444 (2017).

  9. HIV

    Mapping a path to HIV elimination

    1. Orla M. Smith

    About 25 million people in sub-Saharan Africa are living with HIV. Coburn et al. looked into the design of HIV elimination strategies. They focused on Lesotho, where ∼25% of the population is infected with HIV. They combined several large data sets and constructed a map that revealed the countrywide geographic distribution of HIV-infected people. About 20% live in urban areas, and almost all rural communities have at least one HIV-infected person. The spatial dispersion of Lesotho's population may thus hinder and even prevent the elimination of HIV, and this may hold true for other predominantly rural countries in sub-Saharan Africa.

    Sci. Transl. Med. 9, eaag0019 (2017).

  10. Climate Change

    Consequences of shifting species distributions

    1. Andrew M. Sugden

    Climate change is causing geographical redistribution of plant and animal species globally. These distributional shifts are leading to new ecosystems and ecological communities, changes that will affect human society. Pecl et al. review these current and future impacts and assess their implications for sustainable development goals.

    Science, this issue p. eaai9214

  11. Neurodevelopment

    The epigenetics of face-making

    1. Pamela J. Hines

    How is it that our earlobes are attached to our ears and not our chins? Diverse bits of facial structure are derived from migrating neural crest cells. The cells start out similar but end up building very different facial structures. Neural crest cells destined for one structure can be rerouted to develop others, however. Minoux et al. found that neural crest cells share prepatterned poised chromatin states that are established before the cells migrate and retained during migration. Different developmental programs are unlocked when the migrating cells near their final location and interact with local patterning signals.

    Science, this issue p. eaal2913

  12. Cancer Genomics

    Effects of the tumor microenvironment

    1. Laura M. Zahn

    Glioma brain tumors that carry mutant copies of the IDH gene can be subdivided into two major classes. However, the development of and differences between these two classes are not well characterized. Venteicher et al. coupled bulk sequencing and publicly available data with single-cell RNA sequencing data on glioma patient tissue samples. They identified a common lineage program that is shared between glioma subtypes. This suggests that the observed differences between the two glioma classes originate from lineage-specific genetic changes and the tumor microenvironment.

    Science, this issue p. eaai8478

  13. Martian Atmosphere

    Most of Mars' atmosphere has been lost

    1. Keith T. Smith

    Mars has a thin atmosphere composed mainly of carbon dioxide. Evidence on the planet's surface indicates that Mars was once warmer and wetter, suggesting a thicker atmosphere in the past. Jakosky et al. measured the abundances of argon isotopes at different heights in the atmosphere. Because lighter isotopes are more easily ejected than heavier ones, about 66% of Mars' atmosphere has been lost into space since it formed. Understanding the history of Mars' atmosphere will help explain how and why its climate changed, informing the study of similar processes on Earth.

    Science, this issue p. 1408

  14. Organic Chemistry

    Turning benzene into a C–H bond cleaver

    1. Jake Yeston

    Ask chemists for the best way to break a strong bond, and they will tell you to make an even stronger one. Shao et al. applied this principle by using silicon-fluorine bonds to break carbon-hydrogen bonds. They prepared benzene rings with adjacent fluorine and silicon substituents. Then they used a little extra activated silicon, paired with a carborane, to prime a cycle that draws away the fluorine to produce a cation-like aryl intermediate. This intermediate can then slice through the typically inert C–H bonds in alkanes, including methane. The alkylated rings go on to release their silicon, which keeps the process going.

    Science, this issue p. 1403

  15. Phylogenetics

    Photosynthesis evolution in Cyanobacteria

    1. Laura M. Zahn

    How and when Cyanobacteria evolved the ability to produce oxygen through photosynthesis is poorly understood. Soo et al. examined the genomes of Cyanobacteria and other related bacterial lineages. The phylogenetic relationships of these prokaryotes suggest that the evolution of aerobic respiration likely occurred multiple times. This, along with evidence that the modern photosynthetic system apparently arose through the lateral gene transfer and fusion of two photosynthetic systems, supports a relatively late origin of photosynthesis in evolutionary history.

    Science, this issue p. 1436

  16. Infectious Disease

    Mtb faces sirtuin death

    1. Angela Colmone

    New therapies are needed to combat Mycobacterium tuberculosis (Mtb), which is a poster child for drug resistance. Now, Cheng et al. report that Mtb infection down-regulates sirtuin 1, a NAD+ (oxidized nicotinamide adenine dinucleotide)–dependent deacetylase, in myeloid cells in animal models and patients with active disease. Activating sirtuin 1 inhibited intracellular growth of Mtb; it also inhibited persistent inflammatory responses, which decreased lung pathology. Furthermore, sirtuin 1 activation enhanced the efficacy of a first-line antituberculosis drug. These effects may have been due in part to myeloid cell modulation, because mice with myeloid cell–specific sirtuin 1 deficiency had both increased inflammation and higher susceptibility to infection than wild-type controls. Thus, sirtuin 1 may be a target for host-directed therapy for Mtb.

    Sci. Immunol. 2, eaaj1789 (2017).

  17. Conservation

    Flying foxes in peril

    1. Julia Fahrenkamp-Uppenbrink

    Island flying foxes, a group of fruit bats found on many tropical islands, are increasingly under threat from hunting and habitat destruction. In a Perspective, Vincenot et al. draw attention to the important ecological roles that these species play. For example, the last surviving flying fox species on Mauritius is key to the survival of the native flora on the island. Yet flying foxes are widely seen as vermin, and conflicts with fruit growers have led to culls. The authors call for improved laws, stricter enforcement, and the use of nonlethal “flying fox–friendly” methods for protecting fruit crops to avoid further loss of these keystone species.

    Science, this issue p. 1368

  18. Neuroscience

    Vitamin C prevents microglia activation

    1. Annalisa VanHook

    Changes in the levels of ascorbate, the reduced form of vitamin C, alter neuronal function and are associated with neurodegenerative disorders. Activation of microglia in response to tissue damage or pathogens also contributes to neurodegenerative disease. Portugal et al. showed that reducing vitamin C uptake through the sodium–vitamin C cotransporter 2 (SVCT2) triggered the activation of primary rodent and human microglia. Microglia activation was suppressed by ascorbate treatment or when SVCT2 internalization was blocked, suggesting that ascorbate could be used to keep microglia from becoming reactive.

    Sci. Signal. 10, eaal2005 (2017).

  19. Catalysis

    Supported gold ions

    1. Phil Szuromi

    The mercuric chloride catalyst for acetylene hydrochlorination creates vinyl chloride, an important polymer feedstock. However, a more environmentally friendly catalyst of gold supported on carbon can now replace mercuric chloride. Malta et al. used x-ray spectroscopic studies of the working catalysts and computational modeling to show that the active species are coexisting single-site Au+ and Au3+ cations. These species are analogs of soluble catalysts with single metal atoms that react via a similar redox couple.

    Science, this issue p. 1399